Cell-derived exosomes make cell-based therapy more clinically controllable

Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events.

As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable.

Proposed scheme for the clinical application of CAR-T cell-derived exosomes. Peripheral blood sample (30-50 ml) is taken from cancer patient. Total nucleated cells are isolated through density separation or red blood cell lysate solution and cultured with T cell stimulators, such as antibodies for CD3 and CD28. CD8+ T cells are selected through positive or negative selection method and transfected with CARs through viral or non-viral transfection technology. CAR-engineered T cells are ex vivo expanded in the presence of IL-2. CAR-T cell-derived exosomes are isolated from culture media as described in the text. Exosomes are characterized by biomarker assessment and quantified by protein assay. Exosomes are infused into the same patient after preconditioning with chemotherapy.